Carboplatin treatment of antiestrogen-resistant breast cancer cells

Abstract

Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen-resistant breast cancer cell lines have increased sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen-resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression was correlated with increased carboplatin response in the tamoxifen-resistant cell line MCF-7/TAMR-1 and overexpression of Bcl-2 in this cell line resulted in significantly reduced carboplatin sensitivity, confirming the anti-apoptotic role of Bcl-2. However, neither Bcl-2 expression alone, nor Bcl-2 in combination with Bcl-xL and Bax, could explain the observed responses to carboplatin in all tamoxifen-resistant cell lines, indicating that more markers are needed to predict the response to carboplatin in tamoxifen-resistant breast cancer.